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Synlett 2002(12): 2080-2082
DOI: 10.1055/s-2002-35562
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of a New Potential Chelating Agent for Radioimmunotherapy

Sébastien G. Gouina,b, Jean-François Gestinb,c, Patricia Remaudb, Alain Faivre-Chauvetb, Jean Claude Meslina, David Deniaud*a
a Laboratoire de Synthèse Organique, UMR CNRS 6513, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44072 Nantes Cedex, France
b INSERM U463, Chimie des bioconjugués, 9 quai Moncousu, 44093 Nantes Cedex, France
Fax: +33(251)125402; e-Mail: david.deniaud@chimie.univ-nantes.fr;
c CHELATEC SAS, Institut de Biologie, 9 quai Moncousu, 44093 Nantes Cedex, France
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Publication History

Received 16 July 2002
Publication Date:
20 November 2002 (online)

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Abstract

The synthesis of a new rigid analogue of cyclohexyl-TTHA, an efficient lanthanide ligand, as well, as the first complexation trials are reported. This polyaminopolycarboxylic acid, Ph-DTHA 1, was obtained in five steps from phenylenediamine as starting product. The key intermediate was phenylenediethylenetetraamine 4, which after alkylation and hydrolysis gave the expected compound 1 with ten coordination centers.

Key words

ligands - polyaminopolycarboxylic acids - radioimmunotherapy - complexes - radionuclides

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15

Spectrum data of compound 1: IR (KBr): 3419, 2970, 1733, 1635, 1418, 1256 cm-1; 1H NMR (200 MHz, D2O): δ = 3.49 [4 H, m, 2 × NCH2CH 2N(CH2CO2H)2], 3.69 (4 H, m, 2 × NCH 2CH2N(CH2CO2H)2), 4.09 [4 H, s, 2 × N(CH 2CO2H)], 4.19 [8 H, s, 2 × N(CH 2 CO2H)2], 7.13 (4 H, m, CHar);
13C NMR (50 MHz, D2O): δ = 50.4 [2 × NCH2 CH2N(CH2CO2H)2], 56.5 [2 × NCH2CH2N(CH2CO2H)2], 57.3 [2 × N(CH2CO2H)], 58.5 [2 × N(CH2CO2H)2], 125.7 [2 × CHar], 128.8 [2 × CHar], 145.0 [2 × Car], 171.9 [4 × N(CH2 CO2H)2], 178.2 [2 × N(CH2 CO2H)]; MS (ES+): = 543.1 (M + H+), 565.1 (M + Na+); mp >300 °C.